Project Summary: Dementia has a high global prevalence due to the aging population, places an enormous burden on health care systems. Alzheimer's disease (AD) is the most common cause of dementia, and it is widely believed that the accumulation of Amyloid beta (A?) peptide is a key event in the pathogenesis of AD, representing preclinical disease stages. Cerebral iron is strongly implicated as a cofactor in the pathogenesis of AD, and its overload accelerates A? production and promotes the toxicity of the A? peptide. However, the impact of brain iron load on cognitive performance and prevalence of regional A?-plaque-load in AD and its precursor, mild cognitive impairment (MCI), is lacking. Our overall aim is to study the role of brain iron load in the development of cognitive decline, MCI and dementia, in particular AD. We are uniquely positioned to carry out this project in the Atherosclerosis Risk in Communities (ARIC) study, which has collected clinical data from cohort participants over the past 30 years. A biracial sample of elderly adults was evaluated by brain MRI and cognitive tests at study visit 5 with repeat testing underway at visit 6. We will utilize the often-discarded phase signal from gradient echo MRI data at visit 6 (n=1,000) to compute quantitative susceptibility mapping (QSM). Brain iron load will be automatically quantified using our recent developed susceptibility multi-atlas tool. Accordingly, we propose to determine the contribution of cerebral iron load in ARIC participants based on QSM approach with the following specific aims. Aim 1: Establish if increased cerebral iron measures are independently associated with dementia or mild cognitive (MCI) in ARIC participants aged 73-94 years. Aim 2: To relate known midlife dementia risk factors and dietary intake with cerebral iron load measured late-life.